Ribosomal protein S7 ubiquitination during ER stress in yeast is associated with selective mRNA translation and stress outcome.

eIF2a phosphorylation-mediated translational regulation is crucial for global translation repression by various stresses, including the unfolded protein response (UPR). However, translational control during UPR has not been demonstrated in yeast. This study investigated ribosome ubiquitination-mediated translational controls during UPR. Tunicamycin-induced ER stress enhanced the levels of ubiquitination of the ribosomal proteins uS10, uS3 and eS7. Not4-mediated monoubiquitination of eS7A was required for resistance to tunicamycin, whereas E3 ligase Hel2-mediated ubiquitination of uS10 was not. Ribosome profiling showed that the monoubiquitination of eS7A was crucial for translational regulation, including the upregulation of the spliced form of HAC1 (HAC1i) mRNA and the downregulation of Histidine triad NucleoTide-binding 1 (HNT1) mRNA. Downregulation of the deubiquitinating enzyme complex Upb3-Bre5 increased the levels of ubiquitinated eS7A during UPR in an Ire1-independent manner. These findings suggest that the monoubiquitination of ribosomal protein eS7A plays a crucial role in translational controls during the ER stress response in yeast. Overall design: 2~4 different Tm treatment in 3 different strains. 1µg/ml Tunicamycin (Tm) was added into the growing cell culture at log phase, and harvested the cell at the following time points. WT cells were harvested at 0, 1, 2, 4 hour after Tunicamycin treatment. eS7-WT and eS7-4KR cells were harvested at 0 and 4 hour after Tunicamycin treatment.